[Is JAK inhibition an option in the treatment of interstitial lung disease in rheumatoid arthritis?] / Ist JAK-Hemmung eine Option in der Behandlung der interstitiellen Lungenerkrankung bei einer rheumatoiden Arthritis?

A 69-year-old male patient with seropositive erosive rheumatoid arthritis (RA) presented to our clinic due to progressive dyspnea. High-resolution computed tomography (HRCT) and immunological bronchioalveolar lavage revealed ground-glass opacities and a lymphocytic alveolitis caused by interstitial lung disease (ILD) in RA. Considering previous forms of treatment, disease-modifying antirheumatic drug (DMARD) treatment was switched to tofacitinib. Tofacitinib treatment demonstrated a 33% reduction in ground-glass opacities by artificial intelligence-based quantification of pulmonary HRCT over the course of 6 months, which was associated with an improvement in dyspnea symptoms. In conclusion, tofacitinib represents an effective anti-inflammatory therapeutic option in the treatment of RA-ILD.

Assessing the diagnostic value of a potential screening tool for detecting early interstitial lung disease at the onset of inflammatory rheumatic diseases.

BACKGROUND: Interstitial lung disease (ILD) is a severe pulmonary complication in inflammatory rheumatic diseases (IRD) and associated with significantly increased morbidity and mortality. That is why ILD screening at a very early stage, at the onset of IRD, is essential. The objective of the present study was to evaluate the diagnostic value and utility of a stepwise approach as a potential ILD screening tool in patients with newly diagnosed IRD. METHODS: Consecutively, 167 IRD patients were enrolled. To homogenize the study cohort, an age and gender matching was performed. The case-control study included 126 patients with new onset of IRD (mainly connective tissue diseases [CTD], small vessel vasculitis, and myositis). We applied a stepwise screening algorithm in which all patients underwent pulmonary function testing (PFT) and/or additional chest radiography. If there was at least one abnormal finding, pulmonary high-resolution computed tomography (HRCT) was subsequently performed. RESULTS: With our stepwise diagnostic approach, we identified 63 IRD patients with ILD (ILD group) and 63 IRD patients without ILD (non-ILD group). A reduced diffusing capacity for carbon monoxide (DLCO) < 80% showed a sensitivity of 83.6% and a specificity of 45.8% compared to chest X-ray with 64.2% and 73.6%, respectively, in detecting ILD. The combination of reduced DLCO and chest X-ray revealed a sensitivity of 95.2% and a specificity of 38.7%. The highest sensitivity (95.2%) and specificity (77.4%) were observed for the combination of reduced DLCO, chest X-ray, and pulmonary HRCT. The most common pulmonary abnormalities on HRCT were ground-glass opacities (GGO; 36.5%), followed by non-specific interstitial pneumonia (NSIP; 31.8%) and usual interstitial pneumonia (UIP; 9.5%). CONCLUSIONS: The combination of reduced DLCO (< 80%), chest X-ray, and pulmonary HRCT yielded the highest sensitivity and specificity in detecting ILD at the onset of IRD. Therefore, this stepwise approach could be a new screening algorithm to identify IRD patients with pulmonary involvement already at the time of the initial IRD diagnosis.

Diagnosing lung involvement in inflammatory rheumatic diseases-Where do we currently stand?

Lung involvement is the most common and serious organ manifestation in patients with inflammatory rheumatic disease (IRD). The type of pulmonary involvement can differ, but the most frequent is interstitial lung disease (ILD). The clinical manifestations of IRD-ILD and severity can vary from subclinical abnormality to dyspnea, respiratory failure, and death. Consequently, early detection is of significant importance. Pulmonary function test (PFT) including diffusing capacity of the lungs for carbon monoxide (DLCO), and forced vital capacity (FVC) as well as high-resolution computed tomography (HRCT) are the standard tools for screening and monitoring of ILD in IRD-patients. Especially, the diagnostic accuracy of HRCT is considered to be high. Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) allow both morphological and functional assessment of the lungs. In addition, biomarkers (e.g., KL-6, CCL2, or MUC5B) are being currently evaluated for the detection and prognostic assessment of ILD. Despite the accuracy of HRCT, invasive diagnostic methods such as bronchoalveolar lavage (BAL) and lung biopsy are still important in clinical practice. However, their therapeutic and prognostic relevance remains unclear. The aim of this review is to give an overview of the individual methods and to present their respective advantages and disadvantages in detecting and monitoring ILD in IRD-patients in the clinical routine.

Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

OBJECTIVES: Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. METHODS: We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. RESULTS: ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P < 0.0001), more frequently had cutaneous manifestations (63% vs 38% and 34%, P = 0.03) and pulmonary nodules (25% vs 10% and 8%, P = 0.046), and lower median eosinophil count (1450 vs 5400 and 3224/mm3, P < 0.0001). Vasculitis relapse-free survival was shorter for PR3-ANCA (hazard ratio 6.05, P = 0.005) and MPO-ANCA patients (hazard ratio 1.88, P = 0.0002) compared with ANCA-negative patients. CONCLUSION: PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.

Organ Manifestation and Systematic Organ Screening at the Onset of Inflammatory Rheumatic Diseases.

BACKGROUND: Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare. To close this knowledge gap, this cross-sectional study was initiated to evaluate the extent of solid organ manifestations in newly diagnosed IRD patients, and to present a structured systematic organ screening algorithm. MATERIALS AND METHODS: The study included 84 patients (63 women, 21 men) with newly diagnosed IRD. None of the patients received any rheumatic therapy. All patients underwent a standardised organ screening programme encompassing a basic screening (including lungs, heart, kidneys, and gastrointestinal tract) and an additional systematic screening (nose and throat, central and peripheral nervous system) on the basis of clinical, laboratory, and immunological findings. RESULTS: Represented were patients with connective tissue diseases (CTD) (72.6%), small-vessel vasculitis (16.7%), and myositis (10.7%). In total, 39 participants (46.5%) had one or more organ manifestation(s) (one organ, 29.7%; two organs, 10.7%; ≥three organs, 6.0%). The most frequently involved organs were the lungs (34.5%), heart (11.9%), and kidneys (8.3%). Lastly, a diagnostic algorithm for organ manifestation was applied. CONCLUSION: One-half of the patients presented with a solid organ involvement at initial diagnosis of IRD. Thus, in contrast to what has been described in the literature, organ manifestations were already present in a high proportion of patients at the time of diagnosis of IRD rather than after several years of disease. Therefore, in IRD patients, systematic organ screening is essential for treatment decisions.

Still Fighting for Breath: a patient survey of the challenges and impact of severe asthma.

We conducted a large global survey, Still Fighting for Breath, in patients with severe persistent asthma, 10 years after the Fighting for Breath survey to assess the impact of disease on patients' lives and to determine if control and management have changed in recent years. Data were collected from 1333 adults (aged >18 years) and caregivers of children (aged 6-17 years) with severe persistent asthma from nine countries through an online survey conducted in 2016 by GfK. A decade after the first survey, our results showed that the impact of severe asthma has not changed significantly and a high proportion of patients with severe asthma remain inadequately controlled. A large discrepancy was observed between the proportion of patients who perceived their asthma to be well controlled (42%) and the proportion of patients who reported to be well controlled as per the Global Initiative for Asthma (GINA) assessment (6%). Although most patients perceived their asthma to be controlled, many experienced frequent symptoms that affected their daily lives. Thus, there is a need for improved management (support and strategies) of patients with severe persistent asthma and improved coordination of efforts that would enable these patients to achieve better disease control.

Interferon-α for Induction and Maintenance of Remission in Eosinophilic Granulomatosis with Polyangiitis: A Single-center Retrospective Observational Cohort Study.

OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by frequent relapses following induction therapy. Interferon-α (IFN-α) can reverse the underlying Th2-driven immune response and has successfully induced remission in previous reports. We undertook this study to investigate its efficacy and safety in patients with EGPA. METHODS: We conducted a retrospective monocentric cohort study including 30 patients (16 women) with active EGPA under IFN-α treatment. Primary endpoints were remission induction, occurrence of relapses, prednisolone (PSL) dosage at time of remission, and adverse events. Remission was defined by a Birmingham Vasculitis Activity Score (BVAS) of 0. Pulmonary function tests were recorded at baseline and at time of remission. Health-related quality of life was analyzed by questionnaire at baseline and following 12 months of treatment. RESULTS: At baseline, the median BVAS was 6 (interquartile range 4-13.5) and remission or partial response was achieved in 25/30 patients. After initiation of IFN-α treatment, the median PSL dosages could be reduced from 17.5 mg/day at baseline to 5.5 mg/day at time of remission. Following remission, 17 relapses (5 major) in 16 patients were observed. Pulmonary function tests improved and the time of hospitalization decreased. Adverse events at initiation of treatment were common, but mostly transient. Severe adverse events occurred during treatment in 4 patients (autoimmune hepatitis, n = 1; drug-induced neuropathy, n = 3). CONCLUSION: IFN-α treatment results in high rate of remission and maintenance in EGPA with significant reduction in oral corticosteroids, although reversible adverse events may occur. IFN-α represents an alternative therapeutic option in cases of refractory to standard treatment.

Anthracofibrosis Manifesting as False-Positive Iodine Accumulation in a Patient With Recent History of Thyroid Carcinoma.

A 33-year-old Indonesian woman presented for follow-up after a recent history of papillary thyroid carcinoma treated with total thyroidectomy and radioiodine therapy. A 131I whole-body scintigraphy showed an elongated iodine accumulation in the right hemithorax. On suspicion of pulmonary metastasis, further diagnostics with 124I PET/CT showed thickening of the bronchial wall and retention of secretion in a middle lobe bronchus. Bronchoscopy and histology allowed a diagnosis of stenosing anthracofibrosis with chronic inflammatory changes.

Lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia: a prospective, multicenter, diagnostic accuracy study.

BACKGROUND: The aim of this prospective, multicenter study was to define the accuracy of lung ultrasound (LUS) in the diagnosis of community-acquired pneumonia (CAP). METHODS: Three hundred sixty-two patients with suspected CAP were enrolled in 14 European centers. At baseline, history, clinical examination, laboratory testing, and LUS were performed as well as the reference test, which was a radiograph in two planes or a low-dose CT scan in case of inconclusive or negative radiographic but positive LUS findings. In patients with CAP, follow-up between days 5 and 8 and 13 and 16 was scheduled. RESULTS: CAP was confirmed in 229 patients (63.3%). LUS revealed a sensitivity of 93.4% (95% CI, 89.2%-96.3%), specificity of 97.7% (95% CI, 93.4%-99.6%), and likelihood ratios (LRs) of 40.5 (95% CI, 13.2-123.9) for positive and 0.07 (95% CI, 0.04-0.11) for negative results. A combination of auscultation and LUS increased the positive LR to 42.9 (95% CI, 10.8-170.0) and decreased the negative LR to 0.04 (95% CI, 0.02-0.09). We found 97.6% (205 of 211) of patients with CAP showed breath-dependent motion of infiltrates, 86.7% (183 of 211) an air bronchogram, 76.5% (156 of 204) blurred margins, and 54.4% (105 of 193) a basal pleural effusion. During follow-up, median C-reactive protein levels decreased from 137 mg/dL to 6.3 mg/dL at days 13 to 16 as did signs of CAP; median area of lesions decreased from 15.3 cm2 to 0.2 cm2 and pleural effusion from 50 mL to 0 mL. CONCLUSIONS: LUS is a noninvasive, usually available tool used for high-accuracy diagnosis of CAP. This is especially important if radiography is not available or applicable. About 8% of pneumonic lesions are not detectable by LUS; therefore, an inconspicuous LUS does not exclude pneumonia.

Omalizumab in patients with severe asthma: the XCLUSIVE study.

BACKGROUND AND AIMS: Although the efficacy and safety of omalizumab (OMA) in uncontrolled severe allergic asthma has been demonstrated in several randomised controlled trials (RCTs), information on the treatment in a practice-related setting is limited. Thus, the purpose of this prospective multi-centre study (XCLUSIVE) was to investigate the efficacy, compliance and utilisation of OMA therapy in real-life clinical practice in Germany. METHODS: One hundred ninety-five asthmatic patients initiated on anti-Immunoglobulin E (IgE) IgE treatment were followed-up for 6 months. Forced expiratory volume in 1 s (FEV(1) ), exacerbation rate, days of absence, asthma symptoms [Asthma Control Questionnaire (ACQ)], a Global Evaluation of Treatment Effectiveness (GETE) and medication use were assessed. RESULTS: Measured outcome variables improved after a 16-week treatment period with OMA (FEV(1) +13.7% predicted P < 0.05, exacerbation rate -74.9% P < 0.0001, days of absence -92.1% P < 0.001, ACQ -43.7% P < 0.0001). Investigators evaluated the effectiveness of OMA by GETE in 78.8% as excellent or good (responder), and in 12.6%/8.6% as moderate/poor or worse (non-responder). Responders demonstrated better improvement of FEV(1), exacerbation rate, days of absence, ACQ and reduction of oral corticosteroids compared with non-responders. CONCLUSION: Results of effectiveness strongly suggest that the efficacy demonstrated in RCTs can be transposed to a clinical practice-related setting.

Current role of emergency ultrasound of the chest.

OBJECTIVE: Chest sonography has gained clinical significance in the diagnosis of various pulmonary, pleural, cardiac, and mediastinal emergency conditions. Therefore, the current role of emergency ultrasound are assessed. DATA SOURCE: A systematic literature search of MEDLINE database was performed to identify all studies dealing with transthoracic sonography/chest ultrasound in combination with pulmonary embolism, pneumothorax, pneumonia, pleural effusion, pulmonary edema, and lung contusion. The relevant sonographic studies between 1988 and 2010 were evaluated. CONCLUSIONS: The noninvasive ultrasound-based diagnosis is relatively portable permitting the technique to be performed at any time, in any place, and on any patient, an ideal method for emergency conditions. Sonography allows immediate diagnosis of pulmonary embolism, pneumothorax, pneumonia, pleural effusion as well as rib fracture, and it provides a basis for further diagnostic- and treatment-related decisions. The key sonographic features associated with these most common emergency chest diseases are illustrated herein.

Transthoracic sonography in comparison to multislice computed tomography in detection of peripheral pulmonary embolism.

The aim of the study was to compare transthoracic sonography (TS) with multislice computed tomography (MSCT) in the detection of peripheral pulmonary embolism (PE). In addition, the study verified peripheral parenchymal findings visualized by TS and MSCT. A total of 33 patients (16 females, 17 males; mean age = 65.4 years) with symptoms of suspected PE were enrolled in the study. TS and MSCT were undertaken within 24 h of the beginning of clinical PE signs. Ten patients suffered from PE as visualized by MSCT. The sensitivity of TS for detecting PE was 70.0% and the specificity was 69.6%. Preferentially, PE and peripheral parenchymal findings were situated in the lower lobes. Oligemia was the main parenchymal alteration detected by MSCT. TS demonstrated that wedge-shaped consolidations were frequently associated with PE. In addition, localized pleural effusion was a typical finding in the presence of PE for both TS and MSCT. TS had moderate sensitivity and specificity compared with MSCT. Furthermore, the study revealed that PE is often associated with peripheral parenchymal changes, both of which are detectable by TS and MSCT. In case of contraindication with MSCT, TS is a potential technique for diagnosing PE-related parenchymal findings and can serve as an alternative method in the diagnosis of PE. However, a negative result with TS does not rule out a PE.

Cardiac involvement in Churg-Strauss syndrome: impact of endomyocarditis.

Cardiac disease is a major contributor to disease-related death in Churg-Strauss syndrome (CSS). We conducted the current study to determine the prevalence and clinical impact of cardiac involvement in CSS patients. We performed a multicenter, cross-sectional analysis of patients diagnosed with CSS. Cardiac workup included electrocardiography, echocardiography, cardiac magnetic resonance imaging (MRI), and endomyocardial biopsy.We analyzed 49 patients with CSS: 22 patients had clinical evidence of cardiac involvement. A negative antineutrophil cytoplasmic antibodies (ANCA) test and much higher eosinophil counts (9947 vs. 3657/microL, respectively, p < 0.001) distinguished patients with cardiac involvement from those without. Impaired left ventricular function (50%), mild to severe valvular insufficiencies (73%), and pericardial effusions (41%) were common findings in these patients. Endomyocarditis was found in 13 patients (59%) as detected by cardiac MRI, cardiac thrombus formation, and endomyocardial biopsy, and was associated with impaired cardiac function. After a mean follow-up of 47 months, most patients had regained or maintained good cardiac function. However, patients with endomyocarditis had a more severe outcome. Two patients died (61 and 99 mo after diagnosis, respectively), both due to severe cardiomyopathy and heart failure.Cardiac involvement is common in patients with CSS and is associated with the absence of ANCA and high eosinophil counts. Endomyocarditis may represent the most severe manifestation eventually causing fatal outcome. A structured clinical assessment incorporating cardiac imaging with echocardiography and MRI can identify impaired cardiac function and endomyocardial abnormalities.

History of guidelines for the diagnosis and management of asthma: from opinion to control.

The Global Initiative on Asthma (GINA) was launched in 1993 in collaboration with the National Heart, Lung, and Blood Institute, the National Institutes of Health (USA) and the WHO. Its first effort was the production of a consensus report on asthma treatment, which aimed to bridge the gap between the various treatment options and the incorporation and implementation of innovative treatment forms into daily clinical practice. The first report published in 1995, A Global Strategy for Asthma Management and Prevention, has been translated into several languages, widely adopted and provided the foundation for several asthma guidelines worldwide. The GINA and other guidelines were primarily based on consensus of expert opinion in order to employ a severity-based classification system as a guide to treatment. However, in the late 1990s, guidelines underwent a major paradigm shift from opinion- to evidence-based classification as the foundation for asthma management. A second major shift involved the classification of asthma according to the level of disease control as a guide to treatment, which was realized for the first time in the revised 2006 GINA guidelines. Since their first appearance, asthma guidelines have played a leading role in disseminating information about asthma. In addition, they have had a substantial impact on standardizing asthma care around the world, which is likely to continue in the future. This article addresses the history of guideline development and issues related to asthma guidelines, with particular emphasis on the GINA guidelines.

Global Initiative for Asthma (GINA) guidelines: 15 years of application.

The Global Initiative for Asthma (GINA), founded in 1993, embodies a network of public health organizations and medical societies, as well as other individuals concerned with asthma. Its first report, published in 1995 and entitled 'A Global Strategy for Asthma Management and Prevention', has been widely adopted, providing the foundation for asthma guidelines in many nations across the world. To this effect, the report has not only been translated into several languages but has also been frequently updated. Since its establishment 15 years ago, GINA has undergone two major paradigm shifts. The first was the change in the late 1990s from an opinion- to an evidence-based approach for the management of asthma severity. The second, an even more radical shift, was seen in 2006, when the revised GINA guidelines involved the classification of asthma severity according to the level of control as a guide to treatment. In order to classify asthma control, elements such as the significance of the partnership between the patient and caregiver, patient education, guided self-management and treatment goals were introduced. In addition to compiling guidelines and reports for the management of asthma, GINA is actively involved in organizing and coordinating the World Asthma Day, regional initiatives and GINA symposia. On the whole, during the 15 years since their original publication in 1995, the GINA guidelines have provided the basis for many national asthma strategies around the world. This course is most likely to continue in the future. In this paper, the history of the development of the guidelines and other issues regarding the GINA project will be addressed.

[Repeated cold water stimulations (hydrotherapy according to Kneipp) in patients with COPD]. / Serielle Kaltwasserreize (Kneipp'scher Oberguss) bei Patienten mit chronisch obstruktiver Bronchitis (COPD).

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from exacerbations caused by infections of the bronchial tract. OBJECTIVE: What effects do hydrotherapeutic applications according to Kneipp have on lung function, blood gases, immune system and quality of life of patients with COPD? PATIENTS AND METHODS: 20 patients with COPD (17 males, 3 females); mean age: 64; forced expiratory volume (FEV1): 62 of 100% (on average); no acute exacerbations, no oral corticosteroids. Measurements were performed (I) at 10 weeks pre-treatment, (II) immediately before therapy (I-II: baseline-period), (III) after 10 weeks treatment with 3 cold affusions and 2 cold washings of the upper part of the body (self-treatment) per week each, (IV) 3 months after completion of the treatment (follow- up). The following parameters were measured: lung function, blood gases, routine lab, experimental lab (interleukines, lymphocytes), maximal expiratory flow (PEF), quality of life and respiratory infections. RESULTS: The pH increased over the course of the study. PEF and the number of lymphocytes significantly increased over the treatment (II-III). Intracellular expression of IL-4 by T lymphocytes decreased. However, the expression of IFN-gamma increased. Frequency of infections was lower during follow-up (IV) than before and during therapy. Quality of life after treatment was estimated to be good in all patients. CONCLUSIONS: Repeated cold stimulations (affusions) can influence the frequency of respiratory infections and improve subjective well-being. It may cause an immunological modulation in terms of the Th1-type pattern.

Sonographic diagnosis and follow-up of pneumonia: a prospective study.

BACKGROUND: Although transthoracic ultrasound offers several important advantages as diagnostic imaging technique in pleural and pulmonary conditions, its significance for the diagnosis and monitoring of pneumonia has yet to be established. OBJECTIVES: To identify sonographic features associated with pneumonia at admission and during the course of the disease under treatment. METHODS: Thirty patients (12 females, 18 males; median age 65.5 years) with X-ray-proven pneumonia underwent transthoracic sonography (TS) on day 0, between days 1 and 3, 4 and 7, 8 and 14, 15 and 21, and after day 21. TS was assessed according to: number, location, shape, echogenicity, echotexture, echostructure, breath-depending movement, size of pneumonic lesions, bronchoaerogram, fluid bronchogram, superficial fluid alveologram, necrotic areas, vascularity and incidence of local and/or basal pleural effusion. RESULTS: Thirty-three pneumonic infiltrates were eligible for analysis in 30 patients. In 57% (17/30), the likely pathogenic microorganism was identified. Pneumonia was recognized as a hypoechoic area of varying size (mean size between 33.7 x 9.38 and 91.2 x 45.3 mm) and shape, with irregular and blurred margins along with a nonhomogeneous echotexture. The most characteristic feature was a positive bronchoaerogram (32/33). Sixty-one percent (20/33) revealed basal and 9% (3/33) local effusion. During follow-up, lesions decreased in size or disappeared (30/33) or decreased in number (4/9). The bronchoaerogram became less pronounced (13/32), basal pleural effusion either diminished (7/20) or dissipated (7/20), as did localized effusion (3/3). In 30 cases, the course of pneumonia was comparable using X-ray and TS. CONCLUSIONS: TS is a noninvasive technique for the diagnosis and follow-up of patients with pneumonia.